Monobactams: A Unique Natural Scaffold of Four-Membered Ring Skeleton, Recent Development to Clinically Overcome Infections by Multidrug- Resistant Microbes

Author(s): Abdel Nasser El-Shorbagi*, Sachin Chaudhary.

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 12 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Monobactam antibiotics have been testified to demonstrate significant antibacterial activity especially the treatment of infections by superbug microbes. Recently, research has been focused on the structural modifications, and new generation of this privileged natural scaffold.

Objective: Efforts have been made to discover the structure-antibacterial relationship of monbactams in order to avoid the aimless work involving the ongoing generated analogues. This review aims to summarize the current knowledge and development of monobactams as a broad-spectrum antibacterial scaffolds. The recent structural modifications that expand the activity, especially in the infections by resistant-strains, combinational therapies and dosing, as well as the possibility of crosshypersensitivity/ reactivity/tolerability with penicillins and cephalosporins will also be summarized and inferred. Different approaches will be covered with emphasis on chemical methods and Structure- Activity Relationship (SAR), in addition to the proposed mechanisms of action. Clinical investigation of monobactams tackling various aspects will not be missed in this review.

Conclusion: The conclusion includes the novels approaches, that could be followed to design new research projects and reduce the pitfalls in the future development of monobactams.

Keywords: Monobactams, antibacterial, multi-resistant strains, penicillins, cephalosporins, structure-activity relationship, clinical investigations.

Boucher, H.W.; Talbot, G.H.; Benjamin, D.K., Jr; Bradley, J.; Guidos, R.J.; Jones, R.N.; Murray, B.E.; Bonomo, R.A.; Gilbert, D. 10 x ’20 Progress-development of new drugs active against gram-negative bacilli: An update from the Infectious Diseases Society of America. Clin. Infect. Dis., 2013, 56(12), 1685-1694.
[] [PMID: 23599308]
Spellberg, B.; Shlaes, D. Prioritized current unmet needs for antibacterial therapies. Clin. Pharmacol. Ther., 2014, 96(2), 151-153.
[] [PMID: 25056396]
Li, B.; Yi, Y.; Wang, Q.; Woo, P.C.; Tan, L.; Jing, H.; Gao, G.F.; Liu, C.H. Analysis of drug resistance determinants in Klebsiella pneumoniae isolates from a tertiary-care hospital in Beijing, China. PLoS One, 2012, 7(7)e42280
[] [PMID: 22860106]
Giske, C.G.; Monnet, D.L.; Cars, O.; Carmeli, Y. Clinical and economic impact of common multidrug-resistant gram-negative bacilli. Antimicrob. Agents Chemother., 2008, 52(3), 813-821.
[] [PMID: 18070961]
Sykes, R.B.; Bonner, D.P. Aztreonam: The first monobactam. Am. J. Med., 1985, 78(2A), 2-10.
[] [PMID: 3871589]
Alván, G.; Nord, C.E. Adverse effects of monobactams and carbapenems. Drug Saf., 1995, 12(5), 305-313.
[] [PMID: 7669260]
Decuyper, L.; Jukič, M.; Sosič, I.; Žula, A.; D’hooghe, M.; Gobec, S. Antibacterial and beta-Lactamase inhibitory activity of monocyclic beta-lactams. Med. Res. Rev., 2018, 38(2), 426-503.
[] [PMID: 28815732]
Tan, L.; Tao, Y.; Wang, T.; Zou, F.; Zhang, S.; Kou, Q.; Niu, A.; Chen, Q.; Chu, W.; Chen, X.; Wang, H.; Yang, Y. Discovery of novel pyridone-conjugated monosulfactams as potent and broad-spectrum antibiotics for multidrug-resistant gram-negative infections. J. Med. Chem., 2017, 60(7), 2669-2684.
[] [PMID: 28287720]
Reck, F.; Bermingham, A.; Blais, J.; Capka, V.; Cariaga, T.; Casarez, A.; Colvin, R.; Dean, C.R.; Fekete, A.; Gong, W.; Growcott, E.; Guo, H.; Jones, A.K.; Li, C.; Li, F.; Lin, X.; Lindvall, M.; Lopez, S.; McKenney, D.; Metzger, L.; Moser, H.E.; Prathapam, R.; Rasper, D.; Rudewicz, P.; Sethuraman, V.; Shen, X.; Shaul, J.; Simmons, R.L.; Tashiro, K.; Tang, D.; Tjandra, M.; Turner, N.; Uehara, T.; Vitt, C.; Whitebread, S.; Yifru, A.; Zang, X.; Zhu, Q. Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae - Identification of LYS228. Bioorg. Med. Chem. Lett., 2018, 28(4), 748-755.
[] [PMID: 29336873]
Khan, A.U.; Maryam, L.; Zarrilli, R. Structure, genetics and worldwide spread of New Delhi metallo-beta-lactamase (NDM): A threat to public health. BMC Microbiol., 2017, 17(1), 101.
Kou, Q.; Wang, T.; Zou, F.; Zhang, S.; Chen, Q.; Yang, Y. Design, synthesis and biological evaluation of C(4) substituted monobactams as antibacterial agents against multidrug-resistant Gram-negative bacteria. Eur. J. Med. Chem., 2018, 151, 98-109.
[] [PMID: 29605810]
Lall, M.S.; Tao, Y.; Arcari, J.T.; Boyles, D.C.; Brown, M.F.; Damon, D.B.; Lilley, S.C.; Mitton-Fry, M.J.; Starr, J.; Stewart, A.M.; Sun, J. Process development for the synthesis of monocyclic β-Lactam Core 17. Org. Process Res. Dev., 2018, 22(2), 212-218.
Horsman, M.E.; Marous, D.R.; Li, R.; Oliver, R.A.; Byun, B.; Emrich, S.J.; Boggess, B.; Townsend, C.A.; Mobashery, S. Whole-genome shotgun sequencing of two beta-proteobacterial species in search of the bulgecin biosynthetic cluster. ACS Chem. Biol., 2017, 12(10), 2552-2557.
[] [PMID: 28937735]
Oliver, R.A.; Li, R.; Townsend, C.A. Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase. Nat. Chem. Biol., 2018, 14(1), 5-7.
[] [PMID: 29155429]
Long, D.H.; Townsend, C.A. Mechanism of integrated beta-lactam formation by a nonribosomal peptide synthetase during antibiotic synthesis. Biochemistry, 2018, 57(24), 3353-3358.
[] [PMID: 29701951]
Rodríguez-Baño, J.; Gutiérrez-Gutiérrez, B.; Machuca, I.; Pascual, A. Treatment of infections caused by extended-spectrum-beta-lactamase-, AmpC-, and carbapenemase-producing Enterobacteriaceae. Clin. Microbiol. Rev., 2018, 31(2), e00079-e17.
[] [PMID: 29444952]
Bush, K.; Page, M.G.P. What we may expect from novel antibacterial agents in the pipeline with respect to resistance and pharmacodynamic principles. J. Pharmacokinet. Pharmacodyn., 2017, 44(2), 113-132.
[] [PMID: 28161807]
Wright, H.; Bonomo, R.A.; Paterson, D.L. New agents for the treatment of infections with Gram-negative bacteria: Restoring the miracle or false dawn? Clin. Microbiol. Infect., 2017, 23(10), 704-712.
[] [PMID: 28893690]
Jorth, P.; McLean, K.; Ratjen, A.; Secor, P.R.; Bautista, G.E.; Ravishankar, S.; Rezayat, A.; Garudathri, J.; Harrison, J.J.; Harwood, R.A.; Penewit, K.; Waalkes, A.; Singh, P.K.; Salipante, S.J. Evolved aztreonam resistance is multifactorial and can produce hypervirulence in Pseudomonas aeruginosa. MBio, 2017, 8(5), e00517-e17.
[] [PMID: 29089424]
Lohans, C.T.; Brem, J.; Schofield, C.J. New Delhi metallo-β-lactamase 1 catalyzes avibactam and aztreonam hydrolysis. Antimicrob. Agents Chemother., 2017, 61(12), e01224-e17.
[] [PMID: 28971873]
Sader, H.S.; Mendes, R.E.; Pfaller, M.A.; Shortridge, D.; Flamm, R.K.; Castanheira, M. Antimicrobial activities of aztreonam-avibactam and comparator agents against contemporary (2016) clinical Enterobacteriaceae isolates. Antimicrob. Agents Chemother., 2017, 62(1), e01856-e17.
[] [PMID: 29061754]
Wenzler, E.; Deraedt, M.F.; Harrington, A.T.; Danizger, L.H. Synergistic activity of ceftazidime-avibactam and aztreonam against serine and metallo-β-lactamase-producing gram-negative pathogens. Diagn. Microbiol. Infect. Dis., 2017, 88(4), 352-354.
[] [PMID: 28602518]
Marshall, S.; Hujer, A.M.; Rojas, L.J.; Papp-Wallace, K.M.; Humphries, R.M.; Spellberg, B.; Hujer, K.M.; Marshall, E.K.; Rudin, S.D.; Perez, F.; Wilson, B.M.; Wasserman, R.B.; Chikowski, L.; Paterson, D.L.; Vila, A.J.; van Duin, D.; Kreiswirth, B.N.; Chambers, H.F.; Fowler, V.G., Jr; Jacobs, M.R.; Pulse, M.E.; Weiss, W.J.; Bonomo, R.A. Can ceftazidime-avibactam and aztreonam overcome beta-lactam resistance Conferred by metallo-beta-lactamases in Enterobacteriaceae? Antimicrob. Agents Chemother., 2017, 61(4), e02243-e16.
[] [PMID: 28167541]
Mojica, M.F.; Papp-Wallace, K.M.; Taracila, M.A.; Barnes, M.D.; Rutter, J.D.; Jacobs, M.R. LiPuma, J.J.; Walsh, T.J.; Vila, A.J.; Bonomo, R.A. LiPuma, J.J.; Walsh, T.J.; Vila, A.J.; Bonomo, R.A., Avibactam restores the susceptibility of clinical isolates of Stenotrophomonas maltophilia to aztreonam. Antimicrob. Agents Chemother., 2017, 61(10), e00777-e17.
[] [PMID: 28784669]
Schalk, I.J.; Mislin, G.L.A. Bacterial iron uptake pathways: Gates for the import of bactericide compounds. J. Med. Chem., 2017, 60(11), 4573-4576.
[] [PMID: 28453272]
Górska, A.; Sloderbach, A.; Marszałł, M.P. Siderophore-drug complexes: Potential medicinal applications of the ‘Trojan horse’ strategy. Trends Pharmacol. Sci., 2014, 35(9), 442-449.
[] [PMID: 25108321]
Möllmann, U.; Heinisch, L.; Bauernfeind, A.; Köhler, T.; Ankel-Fuchs, D. Siderophores as drug delivery agents: Application of the “Trojan Horse” strategy. Biometals, 2009, 22(4), 615-624.
[] [PMID: 19214755]
Saha, M.; Sarkar, S.; Sarkar, B.; Sharma, B.K.; Bhattacharjee, S.; Tribedi, P. Microbial siderophores and their potential applications: A review. Environ. Sci. Pollut. Res. Int., 2016, 23(5), 3984-3999.
[] [PMID: 25758420]
Ji, C.; Juárez-Hernández, R.E.; Miller, M.J. Exploiting bacterial iron acquisition: Siderophore conjugates. Future Med. Chem., 2012, 4(3), 297-313.
[] [PMID: 22393938]
Foley, T.L.; Simeonov, A. Targeting iron assimilation to develop new antibacterials. Expert Opin. Drug Discov., 2012, 7(9), 831-847.
[] [PMID: 22812521]
Wang, Y.; Fu, H.; Li, Y.; Jiang, J.; Song, D. Synthesis and biological evaluation of 8-substituted berberine derivatives as novel anti-mycobacterial agents. Acta Pharm. Sin. B, 2012, 2(6), 581-587.
Patrick, G.L. An introduction to medicinal chemistry, 5th ed; ; Oxford University Press, United Kingdom: Oxford;, 2017.
Lu, W.; Oberthür, M.; Leimkuhler, C.; Tao, J.; Kahne, D.; Walsh, C.T. Characterization of a regiospecific epivancosaminyl transferase GtfA and enzymatic reconstitution of the antibiotic chloroeremomycin. Proc. Natl. Acad. Sci. USA, 2004, 101(13), 4390-4395.
[] [PMID: 15070728]
Bonner, D.P.; Sykes, R.B. Structure activity relationships among the monobactams. J. Antimicrob. Chemother., 1984, 14(4), 313-327.
[] [PMID: 6389473]
Walsh, C. Molecular mechanisms that confer antibacterial drug resistance. Nature, 2000, 406(6797), 775-781.
[] [PMID: 10963607]
Rozenfel’d, G.S. Monocyclic beta-lactam antibiotics. Antibiotics Medical Biotech, 1986, 31(4), 302-315.
Luscher, A.; Moynie, L.; Auguste, P.S.; Bumann, D.; Mazza, L.; Pletzer, D.; Naismith, J.H.; Kohler, T. TonB-dependent receptor repertoire of Pseudomonas aeruginosa for uptake of siderophore-drug conjugates. Antimicrob. Agents Chemother., 2018, 62(6), e00097-e18.
Tillotson, G.S. Trojan horse antibiotics-A novel way to circumvent gram-negative bacterial resistance? Infect. Dis. (Auckl.), 2016, 9, 45-52.
[] [PMID: 27773991]
Klahn, P.; Brönstrup, M. Bifunctional antimicrobial conjugates and hybrid antimicrobials. Nat. Prod. Rep., 2017, 34(7), 832-885.
[] [PMID: 28530279]
Ghosh, M.; Miller, P.A.; Möllmann, U.; Claypool, W.D.; Schroeder, V.A.; Wolter, W.R.; Suckow, M.; Yu, H.; Li, S.; Huang, W.; Zajicek, J.; Miller, M.J. Targeted antibiotic delivery: Selective siderophore conjugation with daptomycin confers potent activity against multidrug resistant Acinetobacter baumannii both in-vitro and in-vivo. J. Med. Chem., 2017, 60(11), 4577-4583.
[] [PMID: 28287735]
Whalan, R.H.; Funnell, S.G.; Bowler, L.D.; Hudson, M.J.; Robinson, A.; Dowson, C.G. Distribution and genetic diversity of the ABC transporter lipoproteins PiuA and PiaA within Streptococcus pneumoniae and related streptococci. J. Bacteriol., 2006, 188(3), 1031-1038.
Ferreira, D.; Seca, A.M.L. C G A, D.; Silva, A.M.S. Targeting human pathogenic bacteria by siderophores: A proteomics review. J. Proteomics, 2016, 145, 153-166.
[] [PMID: 27109355]
Tomaras, A.P.; Crandon, J.L.; McPherson, C.J.; Nicolau, D.P. Potentiation of antibacterial activity of the MB-1 siderophore-monobactam conjugate using an efflux pump inhibitor. Antimicrob. Agents Chemother., 2015, 59(4), 2439-2442.
[] [PMID: 25605364]
Fu, H.G.; Hu, X.X.; Li, C.R.; Li, Y.H.; Wang, Y.X.; Jiang, J.D.; Bi, C.W.; Tang, S.; You, X.F.; Song, D.Q. Design, synthesis and biological evaluation of monobactams as antibacterial agents against gram-negative bacteria. Eur. J. Med. Chem., 2016, 110, 151-163.
[] [PMID: 26827160]
Landman, D.; Singh, M.; El-Imad, B.; Miller, E.; Win, T.; Quale, J. In vitro activity of the siderophore monosulfactam BAL30072 against contemporary Gram-negative pathogens from New York City, including multidrug-resistant isolates. Int. J. Antimicrob. Agents, 2014, 43(6), 527-532.
[] [PMID: 24796217]
van Delden, C.; Page, M.G.; Köhler, T. Involvement of Fe uptake systems and AmpC β-lactamase in susceptibility to the siderophore monosulfactam BAL30072 in Pseudomonas aeruginosa. Antimicrob. Agents Chemother., 2013, 57(5), 2095-2102.
[] [PMID: 23422914]
Livermore, D.M.; Woodford, N. The beta-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter. Trends Microbiol., 2006, 14(9), 413-420.
[] [PMID: 16876996]
Tfifha, M.; Ferjani, A.; Mallouli, M.; Mlika, N.; Abroug, S.; Boukadida, J. Carriage of multidrug-resistant bacteria among pediatric patients before and during their hospitalization in a tertiary pediatric unit in Tunisia. Libyan J. Med., 2018, 13(1)1419047
[] [PMID: 29277142]
European Antimicrobial Resistance Surveillance Network (EARS-Net); 2009.Available from: . http//
Livermore, D.M. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: Our worst nightmare? Clin. Infect. Dis., 2002, 34(5), 634-640.
[] [PMID: 11823954]
Critchley, I.A. Catecholic β-lactams: Facilitated transport. J. Antimicrob. Chemother., 1990, 26(6), 733-735.
[] [PMID: 2081714]
Page, M.G.; Dantier, C.; Desarbre, E. In vitro properties of BAL30072, a novel siderophore sulfactam with activity against multiresistant gram-negative bacilli. Antimicrob. Agents Chemother., 2010, 54(6), 2291-2302.
[] [PMID: 20308379]
Flanagan, M.E.; Brickner, S.J.; Lall, M.; Casavant, J.; Deschenes, L.; Finegan, S.M.; George, D.M.; Granskog, K.; Hardink, J.R.; Huband, M.D.; Hoang, T.; Lamb, L.; Marra, A.; Mitton-Fry, M.; Mueller, J.P.; Mullins, L.M.; Noe, M.C.; O’Donnell, J.P.; Pattavina, D.; Penzien, J.B.; Schuff, B.P.; Sun, J.; Whipple, D.A.; Young, J.; Gootz, T.D. Preparation, gram-negative antibacterial activity, and hydrolytic stability of novel siderophore-conjugated monocarbam diols. ACS Med. Chem. Lett., 2011, 2(5), 385-390.
[] [PMID: 24900319]
Schuff, B.; Mitton-Fry, M.; Arcari, J.; Brown, M.; Casavant, J.; Flanagan, M.; Gerstenberger, B.; Harris, T.; Hoang, T.; Lall, M. Abstracts of Papers. 245th ACS National Meeting & Exposition, New Orleans, LA, United States2013.
Richardson, D.R.; Hefter, G.T.; May, P.M.; Webb, J.; Baker, E. Iron chelators of the pyridoxal isonicotinoyl hydrazone class. III. Formation constants with calcium(II), magnesium(II) and zinc(II). Biol. Met., 1989, 2(3), 161-167.
[] [PMID: 2490071]
Kline, T.; Fromhold, M.; McKennon, T.E.; Cai, S.; Treiberg, J.; Ihle, N.; Sherman, D.; Schwan, W.; Hickey, M.J.; Warrener, P.; Witte, P.R.; Brody, L.L.; Goltry, L.; Barker, L.M.; Anderson, S.U.; Tanaka, S.K.; Shawar, R.M.; Nguyen, L.Y.; Langhorne, M.; Bigelow, A.; Embuscado, L.; Naeemi, E. Antimicrobial effects of novel siderophores linked to beta-lactam antibiotics. Bioorg. Med. Chem., 2000, 8(1), 73-93.
[] [PMID: 10968267]
Link, G.; Ponka, P.; Konijn, A.M.; Breuer, W.; Cabantchik, Z.I.; Hershko, C. Effects of combined chelation treatment with pyridoxal isonicotinoyl hydrazone analogs and deferoxamine in hypertransfused rats and in iron-loaded rat heart cells. Blood, 2003, 101(10), 4172-4179.
[] [PMID: 12511418]
Miethke, M.; Marahiel, M.A. Siderophore-based iron acquisition and pathogen control. Microbiol. Mol. Biol. Rev., 2007, 71(3), 413-451.
[] [PMID: 17804665]
Skaar, E.P. The battle for iron between bacterial pathogens and their vertebrate hosts. PLoS Pathog., 2010, 6(8)e1000949
[] [PMID: 20711357]
Hannauer, M.; Yeterian, E.; Martin, L.W.; Lamont, I.L.; Schalk, I.J. An efflux pump is involved in secretion of newly synthesized siderophore by Pseudomonas aeruginosa. FEBS Lett., 2010, 584(23), 4751-4755.
[] [PMID: 21035449]
Cornelis, P. Iron uptake and metabolism in pseudomonads. Appl. Microbiol. Biotechnol., 2010, 86(6), 1637-1645.
[] [PMID: 20352420]
Hider, R.C.; Kong, X. Chemistry and biology of siderophores. Nat. Prod. Rep., 2010, 27(5), 637-657.
[] [PMID: 20376388]
Budzikiewicz, H. Siderophore-antibiotic conjugates used as trojan horses against Pseudomonas aeruginosa. Curr. Top. Med. Chem., 2001, 1(1), 73-82.
[] [PMID: 11895295]
Page, M.G.; Heim, J. Prospects for the next anti-pseudomonas drug. Curr. Opin. Pharmacol., 2009, 9(5), 558-565.
[] [PMID: 19748829]
Möllmann, U.; Heinisch, L.; Bauernfeind, A.; Köhler, T.; Ankel-Fuchs, D. Siderophores as drug delivery agents: Application of the “Trojan Horse” strategy. Biometals, 2009, 22(4), 615-624.
[] [PMID: 19214755]
Carosso, S.; Liu, R.; Miller, P.A.; Hecker, S.J.; Glinka, T.; Miller, M.J. Methodology for monobactam diversification: Syntheses and studies of 4-thiomethyl substituted beta-lactams with activity against gram-negative bacteria, including carbapenemase producing acinetobacter baumannii. J. Med. Chem., 2017, 60(21), 8933-8944.
[] [PMID: 28994597]
Yoshida, C.; Tanaka, K.; Todo, Y.; Hattori, R.; Fukuoka, Y.; Komatsu, M.; Saikawa, I. Studies on monocyclic beta-lactam antibiotics. IV. Synthesis and antibacterial activity of (3S,4R)-3-[2-(2-aminothiazol-4-yl)-(Z)-2-(O-substituted oxyimino)acetamido]-4-methyl-1- (1H-tetrazol-5-yl)-2-azetidinones. J. Antibiot. (Tokyo), 1986, 39(1), 90-100.
[] [PMID: 3081473]
Han, S.; Zaniewski, R.P.; Marr, E.S.; Lacey, B.M.; Tomaras, A.P.; Evdokimov, A.; Miller, J.R.; Shanmugasundaram, V. Structural basis for effectiveness of siderophore-conjugated monocarbams against clinically relevant strains of Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA, 2010, 107(51), 22002-22007.
[] [PMID: 21135211]
Majewski, M.W.; Watson, K.D.; Cho, S.; Miller, P.A.; Franzblau, S.G.; Miller, M.J. Syntheses and biological evaluations of highly functionalized hydroxamate containing and N-methylthio monobactams as anti-tuberculosis and beta-lactamase inhibitory agents. MedChemComm, 2016, 7(1), 141-147.
[] [PMID: 26918106]
a)Page, M.I. The reactivity of beta-lactams, the mechanism of catalysis and the inhibition of beta-lactamases. Curr. Pharm. Des., 1999, 5(11), 895-913.
[PMID: 10539995]
b)Cherian, P.T.; Deshpande, A.; Cheramie, M.N.; Bruhn, D.F.; Hurdle, J.G.; Lee, R.E. Design, synthesis and microbiological evaluation of ampicillin-tetramic acid hybrid antibiotics. J. Antibiot. (Tokyo), 2017, 70(1), 65-72.
[] [PMID: 27189120]
Chen, D.; Falsetti, S.C.; Frezza, M.; Milacic, V.; Kazi, A.; Cui, Q.C.; Long, T.E.; Turos, E.; Dou, Q.P. Anti-tumor activity of N-thiolated β-lactam antibiotics. Cancer Lett., 2008, 268(1), 63-69.
[] [PMID: 18468785]
Turos, E.; Shim, J.Y.; Wang, Y.; Greenhalgh, K.; Reddy, G.S.K.; Dickey, S.; Lim, D.V. Antibiotic-conjugated polyacrylate nanoparticles: New opportunities for development of anti-MRSA agents. Bioorg. Med. Chem. Lett., 2007, 17(1), 53-56.
[] [PMID: 17049850]
Fischbach, M.A.; Walsh, C.T. Antibiotics for emerging pathogens. Science, 2009, 325(5944), 1089-1093.
[] [PMID: 19713519]
Gaunt, M.J.; Johansson, C.C.; McNally, A.; Vo, N.T. Enantioselective organocatalysis. Drug Discov. Today, 2007, 12(1-2), 8-27.
[] [PMID: 17198969]
MacMillan, D.W. The advent and development of organocatalysis. Nature, 2008, 455(7211), 304-308.
[] [PMID: 18800128]
Pawar, S.A.; Alapour, S.; Khanyase, S.; Cele, Z.E.; Chitti, S.; Kruger, H.G.; Govender, T.; Arvidsson, P.I. Organocatalyzed stereospecific C-C bond formation of β-lactams. Org. Biomol. Chem., 2013, 11(48), 8294-8297.
[] [PMID: 24217690]
Avenoza, A.; Barriobero, J.I.; Busto, J.H.; Peregrina, J.M. Enantiopure synthesis of all four stereoisomers of carbapenam-3-carboxylic acid methyl ester. J. Org. Chem., 2003, 68(7), 2889-2894.
[] [PMID: 12662066]
Salunkhe, D.S.; Piste, P.B. A brief review on recent synthesis of 2-azetidinone derivatives. Int. J. Pharm. Sci. Res., 2014, 5, 666-689.
a)Vazhappilly, C.G.; Saleh, E.; Ramadan, W.; Menon, V.; Al-Azawi, A.M.; Tarazi, H.; Abdu-Allah, H.; El-Shorbagi, A.N.; El-Awady, R. Inhibition of SHP2 by new compounds induces differential effects on RAS/RAF/ERK and PI3K/AKT pathways in different cancer cell types. Invest. New Drugs, 2018, 1-10.
b)El-Shorbagi, A.N.; El-Naggar, M.; Tarazi, H.; Chaudhary, S.; Abdu-Allah, H.; Hersi, F.; Omar, H. Bis-(5-substituted-2-thiono-1,3,5-thiadiazinan-3-yl) butane as a scaffold of anti-proliferative activity, blended by a multicomponent process. Med. Chem. Res., 2018, 27(4), 1103-1110.
c)Abdu-Allah, H.H.; Abdel-Moty, S.G.; El-Awady, R.; El-Shorbagi, A.N. Design and synthesis of novel 5-aminosalicylate (5-ASA)-4-thiazolinone hybrid derivatives with promising antiproliferative activity. Bioorg. Med. Chem. Lett., 2016, 26(7), 1647-1650.
d)El-Shorbagi, A.A.; Abdel-Moty, S.G.; Ahmed, A.N.; Takayama, H.; Kitajima, M.; Aimi, N.; Sakai, S. The antiviral (RNA & DNA) profile of some incomplete C-nucleosides inspired from natural ß-carboline (pyrido [3,4-b] indole) scaffold; pharmacology of the intermediates in the total synthesis. Pharma Chem., 2015, 11, 87-92.
e)El-Shorbagi, A-N.A.; Husein, M.A. Synthesis and investigation of antihypertensive activity using anaesthetizednormotensive nonhuman primates of some 2-aryl-4-(substituted) pyrimido-[1,2-a] benzimidazoles. Pharma Chem., 2015, 7(4), 190-200.
f)El-Shorbagi, A-N.A.; Husein, M.A. An approach to hypertension crisis: Evaluation of new fused banzazoles; 2-arylethenyl and 2,4-bis(arylethenyl) derivatives derived from 2,4-dimethylpyrimido [1,2-a] benzimidazole. Pharma Chem., 2015, 7(5), 319-328.
g)Amin, E.N.; Abdel-Alim, A.A.; Abdel-Moty, S.G.; El-Shorbagi, A.N.; Abdel-Rahman, M.Sh. Synthesis of new 4,5-3(2H)pyridazinone derivatives and their cardiotonic, hypotensive, and platelet aggregation inhibition activities. Arch. Pharm. Res., 2010, 33(1), 25-46.
h)El Bialy, S.A.; Abdelal, A.M.; El-Shorbagi, A.N.; Kheira, S.M. 2, 3-Bis(5-alkyl-2-thiono-1, 3, 5-thiadiazin-3-yl) propionic acid: one-pot domino synthesis and antimicrobial activity. Arch. Pharm. (Weinheim), 2005, 338(1), 38-43.
i)Abdel-Moty, S.G.; Sakai, S.; Aimi, N.; Takayama, H.; Kitajima, M.; El-Shorbagi, A.; Ahmed, A.N.; Omar, N.M. Synthesis of cytotoxic 1-polyhydroxyalkyl-β-carboline derivatives. Eur. J. Med. Chem., 1998, 32(12), 1009-1017.
j)Abd-Elrahman, M.I.; Ahmed, M.O.; Ahmed, S.M. aboul-Fadl, T.; El-Shorbagi, A. Kinetics of solid state stability of glycine derivatives as a model for peptides using differential scanning calorimetry. Biophys. Chem., 2002, 97(2-3), 113-120.
k)Abdu-Allah, H.; Abdelmoez, A.; Tarazi, H.; El-Shorbagi, A-N.; El-Awady, R. Conjugation of 4-aminosalicylate with thiazolinones afforded non-cytotoxic potent in vitro and in vivo anti-inflammatory hybrids. Bioorg. Chem., 2019, 103378
l)Aboul-Fadl, T.; El Shorbagi, A.N. New carriers for representative peptides and peptide drugs. Arch. Pharm. (Weinheim), 1997, 330(11), 327-332.
m)Aboul-Fadl, T.; El-Shorbagi, A.N.; Hozien, Z.A.; Sarhan, A.W. Investigation of alkylating, antineoplastic and anti-HIV potentials of the chalcones: 2-(3-arylpropenoyl)benzimidazole and their corresponding N1-methyl derivatives. Boll. Chim. Farm., 2000, 139(5), 228-234.
n)Aboul-Fadl, T.; Hussein, M.A.; El-Shorbagi, A.N.; Khallil, A.R. New 2H-tetrahydro-1, 3, 5-thiadiazine-2-thiones incorporating glycine and glycinamide as potential antifungal agents. Arch. Pharm. (Weinheim), 2002, 335(9), 438-442.
o)El-Shorbagi, A.N. New tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives as potential antimicrobial agents. Arch. Pharm. (Weinheim), 2000, 333(9), 281-286.
p)Mohamed, M.H.; El-Shorbagi, A-N.A. (±)-termisine, a novel lupine alkaloid from the seeds of Lupinus termis. J. Nat. Prod., 1993, 56(11), 1999-2002.
q)El-Shorbagi, A-N.A.; Sakai, S-I.; El-Gendy, M.A.; Omar, N.; Farag, H.H. Imidazo [2,1-b] benzothiazoles. I. Chem. Pharm. Bull. (Tokyo), 1988, 36(12), 4760-4768.
r)Emara, S.; El-Gindy, A.; El-Shorbagi, A-N.A.; Hadad, G. Utility of copper (II) oxide as a packed reactor in flow injection assembly for rapid analysis of some angiotensin converting enzyme inhibitors. Anal. Chim. Acta, 2003, 489(1), 115-123.
s)Emara, S.; Razee, S.; El-Shorbagi, A-N.; Masujima, T. Flow injection method for the determination of methotrexate with a column-packed oxidizing agent. Analyst (Lond.), 1996, 121(2), 183-188.
t)Abdel-Alim, A.A.; El-Shorbagi, A.N.; Abdel-Moty, S.G.; Abdel-Allah, H.H. Synthesis and anti-inflammatory testing of some new compounds incorporating 5-aminosalicylic acid (5-ASA) as potential prodrugs. Arch. Pharm. Res., 2005, 28(6), 637-647.
[] [PMID: 16042070]
a)Hussein, A.H.; El-Shorbagi, A.A.; Omar, N.M.; Farghaly, Z.S.; Tomioka, K. New chiral amine ligands for enantioselective synthesis of certain (S)-and (R)-monobactams. Bull. Pharm. Sci., 2000, 23(2), 125-136.
bHussein, M.A.; Iida, A.; Tomioka, K. Studies aimed at enhancement of reactivity and enantioselectivity of a lithium ester enolate using a chiral tridentate lithium amide. Tetrahedron, 1999, 55(37), 11219-11228.
Kojo, H.; Mine, Y.; Nishida, M.; Goto, S.; Kuwahara, S. Nature of monocyclic beta-lactam antibiotic Nocardicin A to beta-lactamases. Microbiol. Immunol., 1988, 32(2), 119-130.
[] [PMID: 3287105]
Davidsen, J.M.; Townsend, C.A. In vivo characterization of nonribosomal peptide synthetases NocA and NocB in the biosynthesis of nocardicin A. Chem. Biol., 2012, 19(2), 297-306.
[] [PMID: 22365611]
Mine, Y.; Nonoyama, S.; Kojo, H.; Fukada, S.; Nishida, M.; Nocardicin, A. Nocardicin A, a new monocyclic beta-lactam antibiotic V. In vivo evaluation. J. Antibiot. (Tokyo), 1977, 30(11), 932-937.
[] [PMID: 338567]
Horsman, M.E.; Marous, D.R.; Li, R.; Oliver, R.A.; Byun, B.; Emrich, S.J.; Boggess, B.; Townsend, C.A.; Mobashery, S. Whole-genome shotgun sequencing of Two beta-proteobacterial species in search of the bulgecin biosynthetic cluster. ACS Chem. Biol., 2017, 12(10), 2552-2557.
[] [PMID: 28937735]
Braga, D.; Lackner, G. One Ring to fight them all: The sulfazecin story. Cell Chem. Biol., 2017, 24(1), 1-2.
[] [PMID: 28107651]
Imada, A.; Kitano, K.; Kintaka, K.; Muroi, M.; Asai, M. Sulfazecin and isosulfazecin, novel beta-lactam antibiotics of bacterial origin. Nature, 1981, 289(5798), 590-591.
[] [PMID: 7007891]
Parker, W.L.; O’Sullivan, J.; Sykes, R.B. Naturally occurring monobactams. Adv. Appl. Microbiol., 1986, 31, 181-205.
[] [PMID: 3521210]
Nishida, M.; Mine, Y.; Nonoyama, S.; Kojo, H.; Nocardicin, A. Nocardicin A, a new monocyclic beta-lactam antibiotic III. In vitro evaluation. J. Antibiot. (Tokyo), 1977, 30(11), 917-925.
[] [PMID: 412823]
Kojo, H.; Mine, Y.; Nishida, M.; Nocardicin, A. Nocardicin A, a new monocyclic beta-lactam antibiotic IV. Factors influencing the in vitro activity of Nocardicin A. J. Antibiot. (Tokyo), 1977, 30(11), 926-931.
[] [PMID: 412824]
Nisbet, L.J.; Mehta, R.J.; Oh, Y.; Pan, C.H.; Phelen, C.G.; Polansky, M.J.; Shearer, M.C.; Giovenella, A.J.; Grappel, S.F. Chlorocardicin, a monocyclic beta-lactam from a Streptomyces sp. I. Discovery, production and biological activities. J. Antibiot. (Tokyo), 1985, 38(2), 133-138.
[] [PMID: 3922933]
Li, R.; Oliver, R.A.; Townsend, C.A. Identification and characterization of the sulfazecin monobactam biosynthetic gene cluster. Cell Chem. Biol., 2017, 24(1), 24-34.
[] [PMID: 28017601]
Gaudelli, N.M.; Long, D.H.; Townsend, C.A. β-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis. Nature, 2015, 520(7547), 383-387.
[] [PMID: 25624104]
O’Sullivan, J.; Abraham, E.P. The conversion of cephalosporins to 7 alpha-methoxycephalosporins by cell-free extracts of Streptomyces clavuligerus. Biochem. J., 1980, 186(2), 613-616.
[] [PMID: 7378068]
Box, S.J.; Brown, A.G.; Gilpin, M.L.; Gwynn, M.N.; Spear, S.R. MM 42842, a new member of the monobactam family produced by Pseudomonas cocovenenans. II. Production, isolation and properties of MM 42842. J. Antibiot. (Tokyo), 1988, 41(1), 7-12.
[] [PMID: 3346195]
Sykes, R.B.; Bonner, D.P.; Bush, K.; Georgopapadakou, N.H. Azthreonam (SQ 26,776), a synthetic monobactam specifically active against aerobic gram-negative bacteria. Antimicrob. Agents Chemother., 1982, 21(1), 85-92.
[] [PMID: 6979307]
Kishimoto, S.; Sendai, M.; Hashiguchi, S.; Tomimoto, M.; Satoh, Y.; Matsuo, T.; Kondo, M.; Ochiai, M. Synthesis of sulfazecin-type 2-azetidinones with a carbon substituent at the 4-position. J. Antibiot. (Tokyo), 1983, 36(10), 1421-1424.
[] [PMID: 6358173]
Yoshida, K.; Mitani, M.; Naeshiro, I.; Torii, H.; Tanayama, S. Disposition of carumonam (AMA-1080/Ro 17-2301), a new N-sulfonated monocyclic beta-lactam, in rats and dogs. Antimicrob. Agents Chemother., 1986, 29(6), 1017-1024.
[] [PMID: 3729358]
Imada, A.; Kondo, M.; Okonogi, K.; Yukishige, K.; Kuno, M. In vitro and in vivo antibacterial activities of carumonam (AMA-1080), a new N-sulfonated monocyclic beta-lactam antibiotic. Antimicrob. Agents Chemother., 1985, 27(5), 821-827.
[] [PMID: 3874598]
Kita, Y.; Fugono, T.; Imada, A. Comparative pharmacokinetics of carumonam and aztreonam in mice, rats, rabbits, dogs, and cynomolgus monkeys. Antimicrob. Agents Chemother., 1986, 29(1), 127-134.
[] [PMID: 3729325]
Ng, W.W.; Chau, P.Y.; Leung, Y.K.; Livermore, D.M. In vitro activities of Ro 17-2301 and aztreonam compared with those of other new beta-lactam antibiotics against clinical isolates of Pseudomonas aeruginosa. Antimicrob. Agents Chemother., 1985, 27(5), 872-873.
[] [PMID: 3925877]
McCullough, B.J.; Wiggins, L.E.; Richards, A.; Klinker, K.; Hiemenz, J.W.; Wingard, J.R. Aztreonam for febrile neutropenia in patients with beta-lactam allergy. Transpl. Infect. Dis., 2014, 16(1), 145-152.
[] [PMID: 24119095]
de Vries-Hospers, H.G.; Welling, G.W.; Swabb, E.A.; van der Waaij, D. Selective decontamination of the digestive tract with aztreonam: A study of 10 healthy volunteers. J. Infect. Dis., 1984, 150(5), 636-642.
[] [PMID: 6541674]
McNulty, C.A.; Garden, G.M.; Ashby, J.; Wise, R. Pharmacokinetics and tissue penetration of carumonam, a new synthetic monobactam. Antimicrob. Agents Chemother., 1985, 28(3), 425-427.
[] [PMID: 4073864]
Wise, R.; Gillett, A.P.; Cadge, B.; Durham, S.R.; Baker, S. The influence of protein binding upon tissue fluid levels of six beta-lactam antibiotics. J. Infect. Dis., 1980, 142(1), 77-82.
[] [PMID: 7400630]
Fracasso, M.E.; Consolo, V.; Ferronato, G.; Leone, R.; Cuzzolin, L.; Benoni, G. Aztreonam penetration of bone and soft tissue, after I.V. infusion and bolus injection. J. Antimicrob. Chemother., 1989, 23(3), 465-467.
[] [PMID: 2732130]
Takabayashi, H.; Kuwabara, S. Tissue penetration of aztreonam in obstetrics and gynecology. Jpn. J. Antibiot., 1985, 38(12), 3606-3608.
[PMID: 3834145]
Whitby, M.; Hempenstall, J.; Gilpin, C.; Weir, L.; Nimmo, G. Penetration of monobactam antibiotics (aztreonam, carumonam) into human prostatic tissue. Chemotherapy, 1989, 35(1), 7-11.
[] [PMID: 2721291]
Weidekamm, E.; Stoeckel, K.; Egger, H.J.; Ziegler, W.H. Single-dose pharmacokinetics of Ro 17-2301 (AMA-1080), a monocyclic beta-lactam, in humans. Antimicrob. Agents Chemother., 1984, 26(6), 898-902.
[] [PMID: 6395801]
1-[(1s)-Carboxy-2-(Methylsulfinyl)Ethyl]-(3r)-[(5s)-5-Amino-5- Carboxypentanamido]-(4r)-Sulfanylazetidin-2-One. Available from .
Fuchs, P.C.; Jones, R.N.; Barry, A.L. In vitro antimicrobial activity of tigemonam, a new orally administered monobactam. Antimicrob. Agents Chemother., 1988, 32(3), 346-349.
[] [PMID: 3259122]
Chin, N.X.; Neu, H.C. Tigemonam, an oral monobactam. Antimicrob. Agents Chemother., 1988, 32(1), 84-91.
[] [PMID: 3279906]
Bodey, G.; Reuben, A.; Elting, L.; Kantarjian, H.; Keating, M.; Hagemeister, F.; Koller, C.; Velasquez, W.; Papadopoulos, N. Comparison of two schedules of cefoperazone plus aztreonam in the treatment of neutropenic patients with fever. Eur. J. Clin. Microbiol. Infect. Dis., 1991, 10(7), 551-558.
[] [PMID: 1915397]
Fishman, A.; Chowers, M.; Altaras, M.; Beyth, Y.; Lang, R. Aztreonam plus piperacillin-empiric treatment of neutropenic fever in gynecology-oncology patients receiving cisplatin-based chemotherapy. Eur. J. Gynaecol. Oncol., 1998, 19(2), 126-129.
[PMID: 9611050]
a)Sendai, M.; Hashiguchi, S.; Tomimoto, M.; Kishimoto, S.; Matsuo, T.; Kondo, M.; Ochiai, M. Chemical modification of sulfazecin. Synthesis of 4-(substituted methyl)-2-azetidinone-1-sulfonic acid derivatives. J. Antibiot. (Tokyo), 1985, 38(3), 346-371.
[] [PMID: 4008329]
b)Matsuda, K.; Nakagawa, S.; Nakano, F.; Inoue, M.; Mitsuhashi, S. Structure-activity relations of 4-fluoromethyl monobactams. J. Antimicrob. Chemother., 1987, 19(6), 753-760.
[] [PMID: 3497148]
Poirel, L.; Naas, T.; Guibert, M.; Chaibi, E.B.; Labia, R.; Nordmann, P. Molecular and biochemical characterization of VEB-1, a novel class A extended-spectrum beta-lactamase encoded by an Escherichia coli integron gene. Antimicrob. Agents Chemother., 1999, 43(3), 573-581.
[] [PMID: 10049269]
Paterson, D.L.; Bonomo, R.A. Extended-spectrum beta-lactamases: A clinical update. Clin. Microbiol. Rev., 2005, 18(4), 657-686.
[] [PMID: 16223952]
Logan, L.K.; Hujer, A.M.; Marshall, S.H.; Domitrovic, T.N.; Rudin, S.D.; Zheng, X.; Qureshi, N.K.; Hayden, M.K.; Scaggs, F.A.; Karadkhele, A.; Bonomo, R.A. Analysis of β-lactamase resistance determinants in Enterobacteriaceae from chicago children: A Multicenter Survey. Antimicrob. Agents Chemother., 2016, 60(6), 3462-3469.
[] [PMID: 27021322]
McPherson, C.J.; Aschenbrenner, L.M.; Lacey, B.M.; Fahnoe, K.C.; Lemmon, M.M.; Finegan, S.M.; Tadakamalla, B.; O’Donnell, J.P.; Mueller, J.P.; Tomaras, A.P. Clinically relevant Gram-negative resistance mechanisms have no effect on the efficacy of MC-1, a novel siderophore-conjugated monocarbam. Antimicrob. Agents Chemother., 2012, 56(12), 6334-6342.
[] [PMID: 23027195]
(a) Bains, G.; Freire, E. Calorimetric determination of cooperative interactions in high affinity binding processes. Anal. Biochem., 1991, 192(1), 203-206.
[] [PMID: 2048721]
(b) Dean, C.R.; Barkan, D.T.; Bermingham, A.; Blais, J.; Casey, F.; Casarez, A.; Colvin, R.; Fuller, J.; Jones, A.K.; Li, C.; Lopez, S.; Metzger, L.E., IV; Mostafavi, M.; Prathapam, R.; Rasper, D.; Reck, F.; Ruzin, A.; Shaul, J.; Shen, X.; Simmons, R.L.; Skewes-Cox, P.; Takeoka, K.T.; Tamrakar, P.; Uehara, T.; Wei, J.R. Mode of action of the monobactam LYS228 and mechanisms decreasing in vitro susceptibility in Escherichia coli and Klebsiella pneumoniae. Antimicrob. Agents Chemother., 2018, 62(10), e0200-e0218.
[] [PMID: 30061293]
(c) Reck, F.; Bermingham, A.; Blais, J.; Capka, V.; Cariaga, T.; Casarez, A.; Colvin, R.; Dean, C.R.; Fekete, A.; Gong, W.; Growcott, E.; Guo, H.; Jones, A.K.; Li, C.; Li, F.; Lin, X.; Lindvall, M.; Lopez, S.; McKenney, D.; Metzger, L.; Moser, H.E.; Prathapam, R.; Rasper, D.; Rudewicz, P.; Sethuraman, V.; Shen, X.; Shaul, J.; Simmons, R.L.; Tashiro, K.; Tang, D.; Tjandra, M.; Turner, N.; Uehara, T.; Vitt, C.; Whitebread, S.; Yifru, A.; Zang, X.; Zhu, Q. Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae - Identification of LYS228. Bioorg. Med. Chem. Lett., 2018, 28(4), 748-755.
[] [PMID: 29336873]
(d) Jones, A.K.; Ranjitkar, S.; Lopez, S.; Li, C.; Blais, J.; Reck, F.; Dean, C.R. Impact of Inducible blaDHA-1 on susceptibility of Klebsiella pneumoniae clinical isolates to LYS228 and identification of chromosomal mpl and ampD mutations mediating upregulation of plasmid-borne blaDHA-1 expression. Antimicrob. Agents Chemother., 2018, 62(10), e01202-e01218.
[] [PMID: 30061296]
(e) Blais, J.; Lopez, S.; Li, C.; Ruzin, A.; Ranjitkar, S.; Dean, C.R.; Leeds, J.A.; Casarez, A.; Simmons, R.L.; Reck, F. In vitro activity of LYS228, a novel monobactam antibiotic, against multidrug-resistant enterobacteriaceae. Antimicrob. Agents Chemother., 2018, 62(10), e00552-e18.
[] [PMID: 30038040]
Romano, A.; Gaeta, F.; Valluzzi, R.L.; Caruso, C.; Rumi, G.; Bousquet, P.J. IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of penicillins, monobactams, and carbapenems. J. Allergy Clin. Immunol., 2010, 126(5), 994-999.
[] [PMID: 20888035]
Tateda, K.; Ishii, Y.; Matsumoto, T.; Yamaguchi, K. ‘Break-point Checkerboard Plate’ for screening of appropriate antibiotic combinations against multidrug-resistant Pseudomonas aeruginosa. Scand. J. Infect. Dis., 2006, 38(4), 268-272.
[] [PMID: 16709527]
Araoka, H.; Baba, M.; Takagi, S.; Matsuno, N.; Ishiwata, K.; Nakano, N.; Tsuji, M.; Yamamoto, H.; Seo, S.; Asano-Mori, Y.; Uchida, N.; Masuoka, K.; Wake, A.; Taniguchi, S.; Yoneyama, A. Monobactam and aminoglycoside combination therapy against metallo-beta-lactamase-producing multidrug-resistant Pseudomonas aeruginosa screened using a ‘break-point checkerboard plate’. Scand. J. Infect. Dis., 2010, 42(3), 231-233.
[] [PMID: 20001223]
Chan, W.; Taylor, A.J.; Ellims, A.H.; Lefkovits, L.; Wong, C.; Kingwell, B.A.; Natoli, A.; Croft, K.D.; Mori, T.; Kaye, D.M.; Dart, A.M.; Duffy, S.J. Effect of iron chelation on myocardial infarct size and oxidative stress in ST-elevation-myocardial infarction. Circ. Cardiovasc. Interv., 2012, 5(2), 270-278.
[] [PMID: 22496085]
Voskaridou, E.; Komninaka, V.; Karavas, A.; Terpos, E.; Akianidis, V.; Christoulas, D. Combination therapy of deferasirox and deferoxamine shows significant improvements in markers of iron overload in a patient with β-thalassemia major and severe iron burden. Transfusion, 2014, 54(3), 646-649.
[] [PMID: 23834310]
Uygun, V.; Kurtoglu, E. Iron-chelation therapy with oral chelators in patients with thalassemia major. Hematology, 2013, 18(1), 50-55.
[] [PMID: 23321010]
Choi, J.J.; McCarthy, M.W. Cefiderocol: A novel siderophore cephalosporin. Expert Opin. Investig. Drugs, 2018, 27(2), 193-197.
[] [PMID: 29318906]
Wager, T.T.; Hou, X.; Verhoest, P.R.; Villalobos, A. Central nervous system multiparameter optimization desirability: Application in drug discovery. ACS Chem. Neurosci., 2016, 7(6), 767-775.
[] [PMID: 26991242]
Tsaioun, K.; Blaauboer, B.J.; Hartung, T. Evidence-based absorption, distribution, metabolism, excretion (ADME) and its interplay with alternative toxicity methods. ALTEX, 2016, 33(4), 343-358.
[] [PMID: 27806179]
Tremaine, L.; Brian, W.; DelMonte, T.; Francke, S.; Groenen, P.; Johnson, K.; Li, L.; Pearson, K.; Marshall, J.C. The role of ADME pharmacogenomics in early clinical trials: Perspective of the industry pharmacogenomics working group (I-PWG). Pharmacogenomics, 2015, 16(18), 2055-2067.
[] [PMID: 26616152]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [1305 - 1320]
Pages: 16
DOI: 10.2174/1570180816666190516113202
Price: $65

Article Metrics

PDF: 30
PRC: 2